Major depression is one of the most debilitating mental illnesses of our time, and, after more than 60 years of research, we have only just begun to understand some of the basic concepts of this illness with multiple origins and manifestations. Approximately one-third of all depressed patients do not respond to any first line of antidepressant therapy, demonstrating dramatically how little we still understand about the neurobiological and molecular mechanisms underlying depression and antidepressant treatment response. Our discoveries to date are likely to be just the tip of the iceberg, and much research is thus needed to identify biological pathways to depression in order to develop more effective antidepressant treatments in the future.

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